Targeting cancer stem cells with nanomaterial-based immune systems: Enhancement of CAR-T and NK cell activity against tumors

Chimeric antigen receptor (CAR) T-cell therapy and natural killer (NK) cells represent powerful tools in cancer immunotherapy. However, their efficacy against solid tumors and cancer stem cells (CSCs) remains limited by the complex tumor microenvironment (TME) and CSC resistance mechanisms. This review explores the transformative potential of hybrid immuno-nanomaterials, which integrate nanotechnology with immunotherapy to overcome these barriers. We delve into how these nanomaterials enhance CAR-T cell functions, improve NK cell activation, and specifically target CSCs through precise therapeutic delivery and TME modulation. The discussion covers advancements in non-viral CAR-T manufacturing, multi-receptor NK cell stimulation, and the use of hybrid nanoparticles to disrupt CSC-mediated immunosuppression. While highlighting significant progress, we also address translational challenges, including manufacturing scalability, regulatory hurdles, and long-term safety, advocating for multidisciplinary collaboration to accelerate clinical adoption.